EXCEED THE SPACE PROVIDED. Homeostasis and remodeling of the vessel wall and the formation of new blood vessels by the process of angiogenesis involve complex interactions between endothelial cells, vascular smooth muscle cells and blood-borne bone marrow-derived cells. These interactions are regulated by growth factors and cytokines, their receptors, extracellular matrix components, proteases and lipids. Loss of regulation by any of these mediators may lead to pathologies impairing vascular function. This renewal application to the IDeA Program expands upon the successes of the previous funding period and requests support for this COBRE in Vascular Biology. The goals of application are to 1) support young and early career investigators toward senior investigator status, 2) support and expand Core facilities established in the previous funding period to support ongoing and future needs of COBRE as well as other MMCRI investigators, 3) recruit additional senior investigators to build the right balance of junior and senior investigators to guide the vision and growth of the Center, and 4) to succeed in the vision of nurturing an international recognized Center of Excellence in Vascular Biology that was conceived and initiated in the previous funding period. This application is comprised of five projects: Project 1, Control of vascular fibrosis and collagen deposition by a novel regulator, Cthrc-1\ Project 2, The contribution of smooth muscle cells to the pathology of gastrointestinal stromal tumors; Project 3, SMAD-independent TGF(3 signaling mechanisms in angiogenesis; Project 4, Mechanism of non-classical release of the angiogenesis regulator interleukin 1a;and Project 5, Sprouty action in hematopoietic compartments. Proposed expansion of the program includes recruitment of 1) a junior magnetic resonance imaging scientist, 2) a senior investigator studying vessel-wall related inflammatory mechanisms, and 3) a senior investigator studying mechanisms of arteriogenesis. Projects will be supported by the Protein, Nucleic Acid Analysis, and Cell Imaging Core, the Mouse Transgenic and Magnetic Resonance Imaging Core, and the Cell Culture and Viral Vector Core. It is anticipated that this renewal award will enhance the further growth of the Center that was established by the previous award and will result in a self-sustaining, internationally recognized Center of Vascular Biology.